Cationic amphiphilic Zn-porphyrin with high antifungal photodynamic potency,Photochemical & Photobiological Sciences

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Cationic amphiphilic Zn-porphyrin with high antifungal photodynamic potency
Photochemical & Photobiological Sciences ( IF 2.7 ) Pub Date : 2017-10-10 00:00:00 , DOI: 10.1039/c7pp00143f
Sara Moghnie _{1,

2,

3,

4,

5} , Artak Tovmasyan _{6,

7,

8,

9} , James Craik _{1,

2,

3,

4,

5} , Ines Batinic-Haberle _{6,

7,

8,

9} , Ludmil Benov _{1,

2,

3,

4,

5}

Affiliation

Photodynamic therapy (PDT) is a promising alternative approach particularly attractive for treatment of localized fungal infections. It is based on compounds, photosensitizers (PSs), which when excited with visible light, generate reactive species that ultimately cause cell death. Such species have short lifespans; as a consequence, efficiency and selectivity of the PDT treatment depend mainly on the properties of the PSs. This study is the first to explore the effect of cationic porphyrin-based photosensitizers on Saccharomyces cerevisiae, a member of the fungus kingdom. The study investigates which properties of the PS are essential for efficient antifungal PDT. Cationic Zn(II) meso-tetrakis(N-alkylpyridinium-2-yl)porphyrins (ZnP) with identical tetrapyrrole core and photo-physical properties, but with different substituents at the meso positions of the porphyrin ring were studied. Attaching six-carbon aliphatic chains to the four pyridyl nitrogens at all meso positions to the porphyrin ring produced a highly photo-efficient amphiphilic, water soluble PS, with minimal dark toxicity. It was taken up by the yeast cells and upon illumination suppressed metabolism by inactivating cytoplasmic and mitochondrial enzymes, and compromising plasma membrane barrier function. At low concentrations (up to 5 μM) the tetrahexyl derivative was a much more powerful antifungal agent than the commercially available chlorin e6. The more lipophilic tetraoctyl analog was also highly photo-efficient but displayed strong dark toxicity, presumably due to higher lipophilicity which might affect the lipid bilayer of membranes. Results presented here can assist the design of antifungal agents whose biological action depends on efficient and rapid uptake by the cells.

中文翻译：

具有高抗真菌光动力潜能的阳离子两亲性锌卟啉

光动力疗法（PDT）是一种有前途的替代方法，对局部真菌感染的治疗特别有吸引力。它基于光敏剂（PSs）化合物，当用可见光激发时，它们会产生反应性物种，最终导致细胞死亡。这样的物种寿命短。结果，PDT处理的效率和选择性主要取决于PS的性质。这项研究是第一个探索基于阳离子卟啉的光敏剂对酿酒酵母（Saccharomyces cerevisiae）（真菌王国的成员）的作用的研究。该研究调查了PS的哪些特性对于有效的抗真菌PDT是必不可少的。阳离子Zn（II）内消旋四（N）研究了具有相同的四吡咯核和光物理性质，但在卟啉环的内消旋位置具有不同取代基的-烷基吡啶鎓-2-基）卟啉（ZnP）。在所有内消旋上将六碳脂族链连接到四个吡啶基氮上在卟啉环上的位置产生了高光效率的两亲性，水溶性PS，具有最小的暗毒性。它被酵母细胞吸收，并在光照下通过使细胞质和线粒体酶失活而抑制了新陈代谢，并损害了质膜的屏障功能。在低浓度（最高5μM）下，四己基衍生物是一种比市售的二氢卟酚e6更有效的抗真菌剂。亲脂性更高的四辛基类似物也具有很高的光敏性，但显示出很强的暗毒性，这可能是由于亲脂性较高可能会影响膜的脂质双层。此处提供的结果可帮助设计抗真菌剂，其生物作用取决于细胞有效和快速的吸收。

更新日期：2017-11-08

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